ライフサイエンスコーパス: CaMKIV

1 CaMKIV activates PGC-1alpha largely through the binding

2 CaMKIV and calspermin expression in the testis are stage

3 CaMKIV and CaMKIIalpha respond differently to substituti

4 CaMKIV does not phosphorylate RORalpha or its ligand-bin

5 CaMKIV has been extensively studied in autoimmune diseas

6 CaMKIV inhibition in MRL/lpr mice resulted in significan

7 CaMKIV is a multifunctional protein kinase associated wi

8 CaMKIV is found in multiple tissues, including brain, th

9 CaMKIV is highly enriched in the nucleus and thought to

10 CaMKIV phosphorylates HDAC4 in vitro and promotes its nu

11 CaMKIV protein levels were also increased in the nucleus

12 CaMKIV-mediated nuclear export of Cabin1 is likely to ac

13 CaMKIV-mTOR-dependent autophagy was fundamentally import

14 CaMKIV/Gr-deficient mice exhibited impaired neuronal cAM

15 CaMKIV/Gr-deficient thymocytes exhibited impaired positi

16 onse to an increase in intracellular Ca(2+), CaMKIV binds Ca(2+)/CaM and becomes phosphorylated on T2

17 lterations in other components of the Ca(2+)-CaMKIV signaling cascade: the ratio of phosphorylated to

18 response to sustained activation of a Ca(2+)-CaMKIV signaling pathway, resulting from growth of cultu

19 (2+) /calmodulin-dependent protein kinase 4 (CaMKIV) to control liver cancer cell growth.

20 We treated MRL/lpr mice with KN-93, a CaMKIV inhibitor, starting at week 8 or week 12 of age a

21 STO609 (a CaMKIV kinase inhibitor), KN93 (a CaMKIV inhibitor), or we utilized cells from which CaMKI

22 al Mphi were incubated with either STO609 (a CaMKIV kinase inhibitor), KN93 (a CaMKIV inhibitor), or

23 Using a CaMKIV null mutant mouse, we demonstrate that a loss of

24 concentrations, and releases CaM to activate CaMKIV when calcium level rises.

25 Ionomycin also activates CaMKIV, which, together with p38, induces AP-1.

26 r, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits i

27 ith vectors expressing constitutively active CaMKIV and calcineurin, we have demonstrated that each p

28 signalling pathway via constitutively active CaMKIV prevents nuclear entry of HDAC4 and HDAC4-mediate

29 Acute expression of active CaMKIV or CREB caused an enhancement of both NMDA recept

30 In this study, active CaMKIV was highly expressed within the intestinal epithe

31 Also, CaMKIV deficiency results in impaired long-term depressi

32 thereby terminating autonomous activity and CaMKIV-mediated gene transcription.

33 ach promoter is activated by calcineurin and CaMKIV in a synergistic fashion.

34 vation of gene expression by calcineurin and CaMKIV is common to members of the TNF cytokine family.

35 ed by Ca2+/CaM, and phosphorylates CaMKI and CaMKIV on Thr177 and Thr200, respectively.

36 lease sequencing, established that CaMKI and CaMKIV phosphorylate completely different sites.

37 aMKKalpha and 30-40% identity with CaMKI and CaMKIV themselves.

38 Again, CaMKI and CaMKIV were different, this time in kinetics and stoichi

39 CaMKKbeta activates both CaMKI and CaMKIV when coexpressed in Jurkat T cells as judged by p

40 pendent protein kinases-I and -IV (CaMKI and CaMKIV) also induce hypertrophic responses in cardiomyoc

41 ependent protein kinases I and IV (CaMKI and CaMKIV) are closely related by primary sequence and pred

42 ependent protein kinases I and IV (CaMKI and CaMKIV, respectively) require phosphorylation on an equi

43 its primary downstream substrates, CaMKI and CaMKIV.

44 d examined as a substrate for both CaMKI and CaMKIV.

45 the CaMK cascade, such as CaMKK, CaMKI, and CaMKIV.

46 f primary Mphi isolated from CaMKIV(+/+) and CaMKIV(-/-) mice.

47 (2+)/calmodulin-activated kinases CaMKK2 and CaMKIV are highly expressed in the brain where they play

48 vely, these findings suggest that CaMKK2 and CaMKIV may represent potential targets for hepatic cance

49 d PFC CaMKII but increased PFC CaMKKbeta and CaMKIV levels, suggesting the involvement of PFC CaMK pa

50 nt signaling cascade involving CaMKKbeta and CaMKIV to decrease the sympathetic tone and increase bon

51 CREB and CaMKIV phosphorylation and CREB target gene expression,

52 ations of synapses through the Rap1-MAPK and CaMKIV-CREB pathways, respectively.

53 nally, mutation of Ser301 impaired NMDA- and CaMKIV-stimulated transcription.

54 CaMKIV in the cerebellum, Wild-type (WT) and CaMKIV KO mice were tested with delay eyeblink condition

55 dent protein kinase IV (Camk4; also known as CaMKIV), a multifunctional serine/threonine protein kina

56 ond event, involving protein kinases such as CaMKIV, leads to efficient nuclear export of the HDAC4.1

57 that CaMKK2 serves as a scaffold to assemble CaMKIV with key components of the mammalian target of ra

58 consider the possible implications of axonal CaMKIV in the context of the unique properties of IB4-bi

59 which correlated with an interaction between CaMKIV and HMGB1 and with CaMKIV phosphorylation of HMGB

60 the PGC-1alpha promoter is regulated by both CaMKIV and CnA activity.

61 ave examined the expression patterns of both CaMKIV and calspermin in mouse testis and unexpectedly f

62 Phosphorylation of Ca(2+)/CaM-bound CaMKIV on its activation loop threonine (residue Thr(200

63 9)) to Ser(85) ((80)LNRQLSSGVS(89)) 3:1, but CaMKIV phosphorylating the two sites equally.

64 Transcriptional activation by CaMKIV is orphan receptor selective and does not occur w

65 this regulation and how they are affected by CaMKIV are not known.

66 phosphorylated with similar efficiencies by CaMKIV, whereas the Leu-substituted peptide is preferred

67 e phosphorylation on Ser 133 is increased by CaMKIV following serotonin treatment of hypothalamic exp

68 ORgamma and COUP-TFI are also potentiated by CaMKIV.

69 of orphan receptor-mediated transcription by CaMKIV.

70 activation of CREB-mediated transcription by CaMKIV.

71 in addition to the classical nuclear calcium-CaMKIV-CREB/CBP (cAMP-response element-binding protein/C

72 s and will phosphorylate and activate CaMKI, CaMKIV, and AMP-activated protein kinase.

73 e actions of a CaMK cascade involving CaMKI, CaMKIV or AMPK.

74 ant consequences in the regulation of CaMKI, CaMKIV, protein kinase B, and ERK signaling pathways.

75 eal a previously undefined role for a CaMKK2/CaMKIV cascade involved in cerebellar granule cell devel

76 Here, we demonstrate that CaMKK2/CaMKIV-dependent phosphorylation of cAMP response elemen

77 The CaMKK2/CaMKIV relay is an upstream regulator of the oncogenic m

78 , pathway, and the importance of this CaMKK2/CaMKIV axis in HCC growth is confirmed by the potent gro

79 -dependent regulation of BDNF through CaMKK2/CaMKIV is required for this process.

80 fail to drive transcription, whereas certain CaMKIV mutants that possess constitutive autonomous acti

81 sts in the nucleus and is required to confer CaMKIV responsiveness.

82 e depolarization requires a highly conserved CaMKIV target serine (Ser-513) of the heterogeneous ribo

83 ach abolished FAD PS-associated constitutive CaMKIV and CREB phosphorylation.

84 dulin-dependent protein kinase IV-deficient (CaMKIV(-/-)) mice have been used to investigate the role

85 ults indicate that neural activity-dependent CaMKIV signaling in the neuronal nucleus plays an import

86 as identified in which PP2A dephosphorylates CaMKIV and functions as a negative regulator of CaMKIV s

87 CaMKIV-associated PP2A then dephosphorylates CaMKIV T200, thereby terminating autonomous activity and

88 sponse element-binding protein (a downstream CaMKIV substrate) was reduced by approximately 10-fold,

89 n CaMKIV interaction with O-GlcNAcase during CaMKIV activation.

90 P2A association in cells results in enhanced CaMKIV-mediated gene transcription that is independent o

91 ecreases of 99- and 343- fold in Vmax/Km for CaMKIV and CaMKIIalpha, respectively.

92 uclear translocation, it is not required for CaMKIV to interact with the nuclear adaptor protein, imp

93 neration of autonomous activity required for CaMKIV-mediated transcriptional regulation.

94 to defining an important signaling role for CaMKIV in a subpopulation of T cells, we identify differ

95 The results suggest an important role for CaMKIV in long-term memory in the cerebellum.

96 r, our results support an important role for CaMKIV in nicotine reward, and suggest that CaMKIV has o

97 m activator of CaMKIV, suggesting a role for CaMKIV in signaling though signaling endosomes.

98 which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses.

99 These studies demonstrate a pivotal role for CaMKIV in the regulation of orphan receptor-mediated tra

100 These results support an important role for CaMKIV/Gr in Ca(2+)-regulated neuronal gene transcriptio

101 se results demonstrate an important role for CaMKIV/Gr in sensitizing thymocytes to selection by low-

102 ous activity is necessary and sufficient for CaMKIV-mediated transcription.

103 ntrast, stimulated naive CD4(+) T cells from CaMKIV(-/-) mice show normal CREB phosphorylation, induc

104 e LPS response of primary Mphi isolated from CaMKIV(+/+) and CaMKIV(-/-) mice.

105 Further, CaMKIV mediates affective, but not physical nicotine wit

106 modulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca(2+) signalin

107 modulin-dependent protein kinase type IV/Gr (CaMKIV/Gr), which is enriched in thymocytes.

108 tase calcineurin, and the kinase type IV/Gr (CaMKIV/Gr), which promote transcription by the MEF2 fami

109 However, CaMKIV is not present in heart, and cardiomyocytes expre

110 However, CaMKIV is present in the cytoplasm and axons of subpopul

111 on loop threonine (residue Thr(200) in human CaMKIV) by Ca(2+)/calmodulin-dependent kinase kinase lea

112 This study identifies CaMKIV as being responsible for the increased expression

113 These novel findings may implicate CaMKIV in chromatin remodeling during nuclear condensati

114 the hyperalgesia response are attenuated in CaMKIV -/- mice.

115 found that nicotine reward is attenuated in CaMKIV knockout (-/-) mice, but cocaine reward is enhanc

116 LPS, this phosphorylation was attenuated in CaMKIV(-/-) Mphi.

117 n account for previously reported changes in CaMKIV O-GlcNAc levels observed in cells.

118 Correspondingly, there is an increase in CaMKIV interaction with O-GlcNAcase during CaMKIV activa

119 We have found that in CaMKIV(-/-) mice--which are deficient in a component of

120 n phosphatase 2A, the catalytically inactive CaMKIV proteins interact more avidly with CaM-dependent

121 ependent calcium influx results in increased CaMKIV activity, which acts to decrease nuclear C/EBPbet

122 n-dependent kinase kinase leads to increased CaMKIV kinase activity.

123 e findings demonstrate that activity-induced CaMKIV signaling contributes to CREB/CBP-dependent trans

124 (CaMKII) (P<0.05) and calmodulin kinase IV (CaMKIV) (P<0.05).

125 cium/calmodulin-dependent protein kinase IV (CaMKIV) activation contributes to the pathogenesis of ex

126 cium/calmodulin-dependent protein kinase IV (CaMKIV) activation, and interactions between nuclear fac

127 (2+)/calmodulin-dependent protein kinase IV (CaMKIV) activation, through special CaM kinase responsiv

128 )(+)/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein mediat

129 o on calcium/calmodulin-dependent kinase IV (CaMKIV) and its pseudophosphorylated form can account fo

130 (2+)-calmodulin-dependent protein kinase IV (CaMKIV) are two proteins encoded by the Camk4 gene.

131 cium/calmodulin-dependent protein kinase IV (CaMKIV) has been implicated in the regulation of CRE-dep

132 the role of calmodulin-dependent kinase IV (CaMKIV) in mouse naive CD4+ T-cell activation remains en

133 d by calcium/calmodulin-dependent kinase IV (CaMKIV) in transcriptional activation of TNF family gene

134 activation via Ca(2+)-calmodulin kinase IV (CaMKIV) induces transcriptional regulation of osteoclast

135 cium/calmodulin-dependent protein kinase IV (CaMKIV) is a member of the broad substrate specificity c

136 Calcium/calmodulin-dependent kinase IV (CaMKIV) is a multifunctional serine/threonine kinase tha

137 cium/calmodulin-dependent protein kinase IV (CaMKIV) is a nuclear protein kinase that responds to acu

138 that calcium/calmodulin-dependent kinase IV (CaMKIV) is highly GlcNAcylated in vivo.

139 that calmodulin-dependent protein kinase IV (CaMKIV) is present in c-Kit+ ScaI+ Lin(-/low) hematopoie

140 Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) or CaMKIIdeltaB, both of which localize to the n

141 rough Ca(2+)/calmodulin-dependent kinase IV (CaMKIV) pathway, rather than the mitogen-activated prote

142 cium/calmodulin-dependent protein kinase IV (CaMKIV) phosphorylates the downstream transcription fact

143 (2+)/calmodulin-dependent protein kinase IV (CaMKIV) potentiates RORalpha-dependent transcription 20-

144 tent CREB phosphorylation and CaM kinase IV (CaMKIV) responsible for phosphorylating the CREB coactiv

145 nd activate the Ca(2+)-calmodulin kinase IV (CaMKIV) signaling cascade, resulting in downregulation o

146 Ca(2+)/calmodulin-dependent kinase IV (CaMKIV) was found to be increased in the nucleus of SLE

147 Ca2+-calmodulin-dependent protein kinase IV (CaMKIV), a nuclear enzyme that can phosphorylate and act

148 cium/calmodulin-dependent protein kinase IV (CaMKIV), calcineurin A (CnA), and the transcriptional co

149 cium/calmodulin-dependent protein kinase IV (CaMKIV), determines its subcellular localization.

150 (2+)/calmodulin-dependent protein kinase IV (CaMKIV), the maintenance of cerebellar LTD is abolished.

151 cium/calmodulin-dependent protein kinase IV (CaMKIV), through inhibitory serine phosphorylation of GS

152 lation recruits a fast calmodulin kinase IV (CaMKIV)-dependent pathway that dominates early signaling

153 lear calmodulin-dependent protein kinase IV (CaMKIV)-mediated phosphorylation and activation of the t

154 AT, p38, and calmodulin-dependent kinase IV (CaMKIV).

155 cium/calmodulin-dependent protein kinase IV (CaMKIV).

156 olecule upstream of CaM-dependent kinase IV (CaMKIV).

157 +)/CaM kinase kinase beta and CaM kinase IV (CaMKIV).

158 cium/calmodulin-dependent protein kinase IV (CaMKIV*).

159 calmodulin-dependent protein kinase type IV (CaMKIV) is a key sensory/effector in excitatory synaptic

160 calmodulin-dependent protein kinase type IV (CaMKIV) is highly expressed in cerebellar cortical granu

161 calmodulin-dependent protein kinase type IV (CaMKIV), which translocates to the nucleus upon engageme

162 impaired activation of the downstream kinase CaMKIV/Gr and its substrate, the transcription factor cy

163 e Ca(2+)/calmodulin-dependent protein kinase CaMKIV was first identified in the cerebellum and has be

164 Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later anti

165 )/calmodulin-dependent protein kinase kinase/CaMKIV/CREB pathway appears to be involved in regulating

166 Small molecules that block the kinases CaMKIV (calcium and calmodulin dependent kinase IV) and

167 ue of Neuron, Boyden et al. use mice lacking CaMKIV and Hansel et al. use mice lacking alphaCaMKII to

168 ively-active (ca) forms of nuclear-localized CaMKIV and measured the induction of all three forms of

169 Using male CaMKIV genetically modified mice, we found that nicotine

170 To test this we manipulated CaMKIV signaling in individual neurons using dominant-ne

171 We hypothesize that calpain-mediated CaMKIV proteolysis is an autoregulatory feedback respons

172 gration and trafficking require ROS-mediated CaMKIV activation leading to formation of NFATc3 and Fos

173 In WT mice, CaMKIV activation is associated with increases in expres

174 ta justify the development of small-molecule CaMKIV inhibitors for the treatment of patients with SLE

175 Mutant CaMKIV proteins that are incapable of developing autonom

176 alyzing the behavior of wild-type and mutant CaMKIV proteins in biochemical experiments and cellular

177 CaM kinase II (CaMKII) but not CaMKIV, the major nuclear CaM kinase in hippocampal neur

178 translocation of a CaM shuttle, and nuclear CaMKIV activation.

179 f cytosolic CaMKI, but not CaMKII or nuclear CaMKIV, dramatically decreases axonal outgrowth and bran

180 In IB4+ spinal nerve axons, 20% of CaMKIV was colocalized with the endocytic marker Rab7 in

181 KLS cell failure in the absence of CaMKIV is correlated with increased apoptosis and prolif

182 Additionally, the absence of CaMKIV markedly altered neurotransmission at excitatory

183 hese results indicate that the activation of CaMKIV and CREB are necessary to establish a late phase

184 circuit adaptations caused by activation of CaMKIV and CREB.

185 Activation of CaMKIV is a transient, tightly regulated event requiring

186 lso been repeatedly noted that activation of CaMKIV is accompanied by the generation of Ca(2+)/CaM-in

187 omatic calcium influx, reduced activation of CaMKIV, and an increase in transcription.

188 unt of CaMK kinase (an upstream activator of CaMKIV) protein and mRNA was significantly reduced.

189 ase-kinase (CAMKK), an upstream activator of CaMKIV, suggesting a role for CaMKIV in signaling though

190 A stable and stoichiometric complex of CaMKIV with protein serine-threonine phosphatase 2A (PP2

191 We have recently shown that deletion of CaMKIV has no effect on calspermin expression but does i

192 Ca(2+)/CaM binding-autoinhibitory domain of CaMKIV is required for association of the kinase with PP

193 Here we evaluate nuclear entry of CaMKIV and demonstrate that the protein kinase homology

194 RA down-regulates expression of CaMKIV and one of its upstream activators, CaMKK1 (calmo

195 Re-expression of CaMKIV in Camk4-/- KLS cells results in the rescue of th

196 he expression of a dominant-negative form of CaMKIV (dnCaMKIV) is restricted to the postnatal forebra

197 xpression of a constitutively active form of CaMKIV that also has increased endogenous CaMKII activit

198 s abolished when a dominant inactive form of CaMKIV was expressed in normal T cells.

199 expression of constitutively active forms of CaMKIV and CREB on synaptic function in the rodent hippo

200 We further demonstrate that a fraction of CaMKIV in spermatids is hyperphosphorylated and specific

201 To investigate the function of CaMKIV in the cerebellum, Wild-type (WT) and CaMKIV KO m

202 o understand the physiological importance of CaMKIV, we disrupted the mouse Camk4 gene.

203 However, inactivation of CaMKIV occurs despite the sustained increase in [Ca2+]i

204 he sequential activation and inactivation of CaMKIV.

205 e find this interaction to be independent of CaMKIV.

206 Furthermore, specific inhibition of CaMKIV by chemical means and by a dominant negative muta

207 study was to determine whether inhibition of CaMKIV would improve disease pathology.

208 plied lentivius-mediated RNA interference of CaMKIV to human T cells and found that knockdown of CaMK

209 s shown by the effect of RNA interference of CaMKIV to markedly accelerate RA-dependent up-regulation

210 to human T cells and found that knockdown of CaMKIV abrogates T-cell receptor-mediated transcription

211 ein, is therefore controlled at the level of CaMKIV rather than CaMKK.

212 mutant mouse, we demonstrate that a loss of CaMKIV protects against murine DSS colitis.

213 gnaling pathways may spare spatial memory of CaMKIV/Gr-deficient mice.

214 l means and by a dominant negative mutant of CaMKIV impairs the ionomycin-induced activity of all thr

215 m by which catalytically inactive mutants of CaMKIV exert their "dominant-negative" functions within

216 sigmoid kinetics, rate-limited by paucity of CaMKIV, protecting against saturation of phospho-CREB in

217 e data suggest that CaMKK phosphorylation of CaMKIV may occur in the cytoplasm.

218 We show that phosphorylation of CaMKIV on Thr(200) leads to the generation of a fully Ca

219 p < 0.0001) and prevented phosphorylation of CaMKIV.

220 ted with greater affinity in the presence of CaMKIV.

221 Calpain-mediated proteolysis of CaMKIV is selective, as several other nuclear and non-nu

222 dification participates in the regulation of CaMKIV activation and function, possibly coordinating nu

223 tion and Ca(2+)-dependent down-regulation of CaMKIV were associated with significant alterations in o

224 ablishes nuclear m-calpain as a regulator of CaMKIV and associated signaling molecules under conditio

225 KIV and functions as a negative regulator of CaMKIV signaling.

226 for a significant part of the requirement of CaMKIV during human T-cell activation.

227 The strict Ca2+ requirement of CaMKIV-dependent phosphorylation of cAMP response elemen

228 Given the proposed role of CaMKIV in CREB activation, we hypothesized that CaMKIV m

229 ates nicotine responses; however the role of CaMKIV in nicotine dependence is unknown.

230 is required for the transcriptional roles of CaMKIV, these data suggest that CaMKK phosphorylation of

231 cylation sites located in the active site of CaMKIV can modulate its phosphorylation at Thr-200 and i

232 We conclude that suppression of CaMKIV mitigates disease development in lupus-prone mice

233 1 of CBP was identified as a major target of CaMKIV phosphorylation in vitro and in vivo.

234 protein at serine-133, a proposed target of CaMKIV.

235 CREB with a time course paralleling that of CaMKIV down-regulation.

236 uced activation and nuclear translocation of CaMKIV, which preceded HMGB1 nucleocytoplasmic shuttling

237 nctions downstream of CaMKII but upstream of CaMKIV in a pathway that restricts dendritic complexity.

238 Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-

239 se was demonstrated by its lack of effect on CaMKIV-mediated CREB phosphorylation.

240 tify at least five sites of GlcNAcylation on CaMKIV.

241 n vitro that the absence of either CaMKK2 or CaMKIV disrupts the ability of developing cerebellar gra

242 Reexpression of CaMKK2 or CaMKIV in granule cells that lack CaMKK2 or CaMKIV, resp

243 Furthermore, loss of CaMKK2 or CaMKIV results in decreased CREB phosphorylation (pCREB)

244 CaMKIV in granule cells that lack CaMKK2 or CaMKIV, respectively, restores pCREB and BDNF to wild-ty

245 ellar development in mice null for CaMKK2 or CaMKIV.

246 bition is unaffected by changes in firing or CaMKIV signaling in individual neurons.

247 ndritic growth induced by Ca(2)(+) influx or CaMKIV.

248 tion with CaMKIV were inhibited by STO609 or CaMKIV RNAi.

249 However, Mphi treated with KN93, STO609, or CaMKIV RNAi before LPS showed reduced nucleocytoplasmic

250 Previously, CaMKIV was shown to stably associate with protein serine

251 nase 4 (gene and transcript: CaMK4; protein: CaMKIV) is the nuclear effector of the Ca(2+) /calmoduli

252 Consistent with these roles, CaMKIV is found predominantly in the nucleus of cells in

253 Significantly, CaMKIV/Gr deficiency raised the selection threshold of p

254 Ca(2+)/CaM activates CaMKK and its substrate CaMKIV, the CREB kinase.

255 vation of HEK293 cells, hemagglutinin-tagged CaMKIV GlcNAcylation rapidly decreases, in a manner dire

256 Small molecules targeting CaMKIV activation may provide therapeutic benefit for pa

257 esponses in cardiomyocytes in vitro and that CaMKIV overexpressing mice develop cardiac hypertrophy w

258 transcriptional assays, we demonstrate that CaMKIV autonomous activity is necessary and sufficient f

259 We demonstrate that CaMKIV directly phosphorylates Cabin1, a transcriptional

260 We further demonstrate that CaMKIV expression and localization are unaffected by the

261 Together, these findings demonstrate that CaMKIV plays key roles in the function and development o

262 Collectively, our results demonstrate that CaMKIV promotes the nucleocytoplasmic shuttling of HMGB1

263 studies in rat testes have demonstrated that CaMKIV mRNA is localized to pachytene spermatocytes, whi

264 In germ cells, we find that CaMKIV is associated with the chromatin.

265 n in mouse testis and unexpectedly find that CaMKIV is expressed in spermatogonia and spermatids but

266 KIV in CREB activation, we hypothesized that CaMKIV might be a crucial molecular component in the dev

267 We observed that CaMKIV was expressed strongly in the cytoplasm and axons

268 We further show that CaMKIV activates the transcription factor MEF2 through a

269 These studies show that CaMKIV is a regulator of HSC homeostasis and suggest tha

270 CaMKIV in nicotine reward, and suggest that CaMKIV has opposing roles in nicotine and cocaine reward

271 The CaMKIV null mice displayed locomotor defects consistent

272 The CaMKIV-associated PP2A then dephosphorylates CaMKIV T200

273 In contrast, the CaMKIV pathway may be well suited to conveying informati

274 tion analysis and found that variants in the CaMKIV gene are associated with a protective effect agai

275 RA-induced repression of the CaMKIV signaling pathway may represent an early event in

276 We demonstrate that inhibition of the CaMKIV/PP2A association in cells results in enhanced CaM

277 3)), fits the expected consensus whereas the CaMKIV site, Ser(24) ((19)SSPALSASAS(28)), is novel.

278 ous ribonucleoprotein L interaction with the CaMKIV-responsive RNA element 1 of stress axis-regulated

279 est that the process may be mediated through CaMKIV-dependent serine phosphorylation of HMGB1.

280 re coregulated in individual neurons through CaMKIV signaling, which is tightly controlled by neurona

281 Thus, CaMKIV-mTOR-dependent autophagy is conserved in both imm

282 ate the importance of autonomous activity to CaMKIV biological function.

283 ns do not inhibit nuclear entry of wild-type CaMKIV but do inhibit the ability of the wild-type prote

284 The ability of wild-type CaMKIV to drive cAMP response element-binding protein-me

285 IV, respectively, suggesting that uncoupling CaMKIV activation from activity generates an error signa

286 Unlike CaMKIV/Gr-deficient mice, the CaMKKalpha mutants exhibit

287 nomous, compensatory synapse elimination via CaMKIV-dependent transcription.

288 lates Ca(2+)-dependent NFATc1 expression via CaMKIV/CREB during inflammatory osteoclastogenesis in th

289 level of phospho-T200 that accumulates when CaMKIV is prevented from interacting with PP2A.

290 Similarly, whereas CaMKIV(+/+) Mphi showed serine phosphorylation of HMGB1

291 Whether CaMKIV also controls inhibitory synaptic scaling and int

292 inhibitor), or we utilized cells from which CaMKIV was depleted by RNA interference (RNAi) before st

293 actors by an NFAT-dependent mechanism, while CaMKIV/Gr selectively and independently activates MEF2D.

294 nteraction between CaMKIV and HMGB1 and with CaMKIV phosphorylation of HMGB1 in vitro.

295 In brain, CaMKKbeta tracks more closely with CaMKIV than does CaMKKalpha.

296 al disease severity directly correlates with CaMKIV activation, as does expression of proinflammatory

297 le for other proteins known to interact with CaMKIV in regulation of its nuclear entry.

298 h HMGB1 phosphorylation and interaction with CaMKIV were inhibited by STO609 or CaMKIV RNAi.

299 while constructs designed to interfere with CaMKIV function attenuated the late phase.

300 es not colocalize to the nuclear matrix with CaMKIV.